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The interplay between DNA topoisomerase 2α post-translational modifications and drug resistance

The type 2 DNA topoisomerases (Top2) are conserved enzymes and biomarkers for cell proliferation. The catalytic activities of the human isoform Top2α are essential for the regulation of DNA topology during DNA replication, transcription, and chromosome segregation. Top2α is a prominent target for an...

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Autores principales: Lotz, Christophe, Lamour, Valérie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: OAE Publishing Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9090595/
https://www.ncbi.nlm.nih.gov/pubmed/35582608
http://dx.doi.org/10.20517/cdr.2019.114
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author Lotz, Christophe
Lamour, Valérie
author_facet Lotz, Christophe
Lamour, Valérie
author_sort Lotz, Christophe
collection PubMed
description The type 2 DNA topoisomerases (Top2) are conserved enzymes and biomarkers for cell proliferation. The catalytic activities of the human isoform Top2α are essential for the regulation of DNA topology during DNA replication, transcription, and chromosome segregation. Top2α is a prominent target for anti-cancer drugs and is highly regulated by post-translational modifications (PTM). Despite an increasing number of proteomic studies, the extent of PTM in cancer cells and its importance in drug response remains largely uncharacterized. In this review, we highlight the different modifications affecting the human Top2α in healthy and cancer cells, taking advantage of the structure-function information accumulated in the past decades. We also overview the regulation of Top2α by PTM, the level of PTM in cancer cells, and the resistance to therapeutic compounds targeting the Top2 enzyme. Altogether, this review underlines the importance of future studies addressing more systematically the interplay between PTM and Top2 drug resistance.
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spelling pubmed-90905952022-05-16 The interplay between DNA topoisomerase 2α post-translational modifications and drug resistance Lotz, Christophe Lamour, Valérie Cancer Drug Resist Review The type 2 DNA topoisomerases (Top2) are conserved enzymes and biomarkers for cell proliferation. The catalytic activities of the human isoform Top2α are essential for the regulation of DNA topology during DNA replication, transcription, and chromosome segregation. Top2α is a prominent target for anti-cancer drugs and is highly regulated by post-translational modifications (PTM). Despite an increasing number of proteomic studies, the extent of PTM in cancer cells and its importance in drug response remains largely uncharacterized. In this review, we highlight the different modifications affecting the human Top2α in healthy and cancer cells, taking advantage of the structure-function information accumulated in the past decades. We also overview the regulation of Top2α by PTM, the level of PTM in cancer cells, and the resistance to therapeutic compounds targeting the Top2 enzyme. Altogether, this review underlines the importance of future studies addressing more systematically the interplay between PTM and Top2 drug resistance. OAE Publishing Inc. 2020-02-27 /pmc/articles/PMC9090595/ /pubmed/35582608 http://dx.doi.org/10.20517/cdr.2019.114 Text en © The Author(s) 2020. https://creativecommons.org/licenses/by/4.0/© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review
Lotz, Christophe
Lamour, Valérie
The interplay between DNA topoisomerase 2α post-translational modifications and drug resistance
title The interplay between DNA topoisomerase 2α post-translational modifications and drug resistance
title_full The interplay between DNA topoisomerase 2α post-translational modifications and drug resistance
title_fullStr The interplay between DNA topoisomerase 2α post-translational modifications and drug resistance
title_full_unstemmed The interplay between DNA topoisomerase 2α post-translational modifications and drug resistance
title_short The interplay between DNA topoisomerase 2α post-translational modifications and drug resistance
title_sort interplay between dna topoisomerase 2α post-translational modifications and drug resistance
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9090595/
https://www.ncbi.nlm.nih.gov/pubmed/35582608
http://dx.doi.org/10.20517/cdr.2019.114
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